It is increasingly recognized that many cardiac arrhythmias can be characterized based on the physical principles of nonlinear dynamics. A nonlinear-dynamical system is one that changes with time (dynamical) and cannot be broken down into a linear sum of its individual components (nonlinear). For certain nonlinear systems, known as chaotic systems, behavior is aperiodic (irregularly irregular) and long-term prediction is impossible, even though the dynamics are entirely deterministic (i.e, the dynamics of the system are completely determined from known inputs and the system's previous state, with no influence from random inputs). Importantly, such determinism can actually be exploited to control the dynamics of a chaotic system. To this end, a variety of chaos-control techniques have been developed and successfully applied to a wide range of physical systems. Such techniques are model-independent, i.e., they require no a priori knowledge of a system's underlying equations, and are therefore appropriate for systems that are essentially “black boxes.”
The success of chaos-control techniques in stabilizing physical systems, together with the fact that many physiological systems are nonlinear-dynamical (e.g., the cardiac conduction system, due to its numerous complex nonlinear component interactions) and lack the detailed analytical system models required for model-based control techniques, have fostered widespread interest in applying these model-independent techniques to biological dynamical systems. In the first such application, Garfinkel et al. (A Garfinkel, M L Spano, W L Ditto, and J N Weiss, “Controlling Cardiac Chaos”, Science, 257:1230-1235, 1992) stabilized drug-induced irregular cardiac rhythms via dynamically-timed electrical stimulation in an in vitro rabbit ventricular-tissue preparation. That work was an important demonstration that the physical principles of chaos control could be extended into the realm of cardiac dynamics.
A later application is described in U.S. Pat. No. 5,836,974 of Christini et al.
The '974 patent describes a technique in which atrioventricular nodal alternans was controlled by monitoring beat-to-beat timing variations in the atrial-His interval (AH) and then eliminating such variations by making beat-to-beat modifications to a His-atrial pacing interval based on the detected variations in AH time interval.
The present invention concerns repolarization alternans, a beat-to-beat alternation in the manner by which the ventricles of the heart repolarize (i.e., return to resting voltage after their depolarization or excitation). As heart rate or pacing rate increases, action potential duration in different regions of the heart first alternates concordantly and then becomes spatially discordant. Such discordance is associated with steep spatial gradients of repolarization that appear to provide the substrate for unidirectional functional block and reentry. This type of alternans is different than the type detected in the aforesaid '974 patent, because that patent describes a technique which approximates AV node conduction rather than relaxation of the ventricle to return to its original state. The repolarization phase of the heartbeat corresponds to the T-wave component of the surface electrocardiogram (ECG). Thus, repolarization alternans (“RPA”), which to date has always been measured via the surface ECG, is often referred to as T-wave alternans (“TWA”). T-wave alternans appears as a beat-to-beat alternation in the amplitude, morphology, or duration of the T-wave. T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, including fibrillation. In fact, T-wave alternans can precede life-threatening arrhythmias and is a risk factor for sudden cardiac death.
T-wave alternans, which usually cannot be detected via beat-by-beat visual analysis, is typically detected via statistical analysis of a large number of consecutive surface ECG beats. (Because of the aggregate nature of such detection, detection of T-wave alternans usually requires at least 5 minutes of ECG acquisition.) One known system which utilizes statistical calculations to infer T-Wave alternans from microvolt surface readings is the Cambridge Heart CH2000 system of Cambridge Heart, Inc., Bedford Mass.
What remains needed in the art is a real-time method for detecting and stabilizing repolarization alternans on a beat-to-beat basis.